Faculty Collaboration Database

Infiltrating T cells during liver graft-versus-host disease show a restricted T-cell repertoire. Biol Blood Marrow Transplant 2000;6(4):408-15

Date

08/05/2000

Pubmed ID

10917576

DOI

10.1016/s1083-8791(00)70017-6

Scopus ID

2-s2.0-0033654791 (requires institutional sign-in at Scopus site)   21 Citations

Abstract

Data from animal models have shown that hepatic graft-versus-host disease (GVHD) may be mediated by donor T cells interacting with liver adhesion molecules, other minor histocompatibility antigens, or both. We hypothesized that T-cell infiltrates within a liver biopsy during clinical GVHD would show a restricted T-cell response because the T cells would be responding to a limited number of antigens. We studied the peripheral T-cell repertoire and the liver-infiltrating T-cell repertoire of a patient who developed skin GVHD and subsequent liver GVHD after a matched sibling bone marrow transplantation for acute myeloid leukemia. Spectratype analysis of peripheral blood at the time of liver GVHD revealed that the patient had reconstituted a complex peripheral T-cell repertoire as evidenced by the presence of complementarity-determining region 3 (CDR3) length heterogeneity in most of the T-cell families. The repertoire complexity was skewed in variable gene beta (VB) 5.3, VB4, VB7, VB8, and VB15. Spectratype analysis on the liver biopsy sample revealed a limited infiltrate with an oligoclonal expansion in VBs 4, 7, and 8. We evaluated the T-cell infiltrate in more detail by sequencing the relevant expansions noted by spectratype and developing probes for the predominant CDR3 sequences. These clonotype probes were hybridized to peripheral blood and liver samples from the patient, a T-cell line developed from the patient's peripheral blood at the time of the initial skin GVHD, the donor's blood and marrow, and control samples. The results showed that the T-cell infiltrate during liver GVHD is mediated by a limited number of T cells, and that those cells are mostly different from the ones expanded from the peripheral blood during an acute skin GVHD reaction. These data support the concept that liver GVHD is a response to tissue-specific minor histocompatibility antigens.

Author List

Margolis DA, Casper JT, Segura AD, Janczak T, McOlash L, Fisher B, Miller K, Gorski J

Authors

David A. Margolis MD Chair, Professor in the Pediatrics department at Medical College of Wisconsin
Annette D. Segura MD Adjunct Assistant Professor in the Pathology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acute Disease
Adolescent
Autoantigens
Bone Marrow Transplantation
Clone Cells
Gene Rearrangement
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Humans
Immunohistochemistry
Leukemia, Myeloid
Liver
Liver Diseases
Male
Receptors, Antigen, T-Cell, alpha-beta
Sequence Analysis, DNA
T-Lymphocytes
Transplantation, Homologous